Synthesis of Morphine

Structure of Morphine

C17H19NO3

Principal investigator	Kenner C. Rice
Publication year	1980
Synthesis type	Total
Number of steps	18 (linear)
References	J. Org. Chem. 1980, 45, 3135. Heterocycles 1977, 6, 1157. J. Med. Chem. 1980, 20, 164.

Part 1 of 1

intermediate structure

+

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200 °C, 2 h, 95%

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POCl3

MeCN

Reflux, 70 min

See the Bischler-Napieralski Reaction

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NaBH3CN

H2O, MeOH

Reflux, 90 min, 86% (2 steps)

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Li

NH3, t-BuOH, THF

-75 to -55 °C, 5.5 h, 90%

See the Birch Reduction

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HCO2Ph

EtOAc

Reflux, 45 min, 94%

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(CH2OH)2, MsOH

THF

RT, 60 min

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N-Bromoacetamide

THF

0-5 °C, 30 min

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HCO2H

H2O

RT, 60 min, 90% (3 steps)

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HF, TfOH, NH4F

H2O

0 °C, 72-96 h, 60%

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HCl

H2O, MeOH

Reflux, 18 h, 98%

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Br2

AcOH

RT, 2 h

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NaOH

CHCl3, H2O

0 °C

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CH2O, H2, NaOAc, Pd/C

AcOH, H2O

79% (3 steps)

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ClCO2Me

PhH

Reflux, 16 h, 100%

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HCl, PhSeCl

EtOAc, H2O

RT, 4.5 h, 85%

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NaIO4

EtOAc, H2O

RT, 20 h, 68%

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LiAlH4

THF

Reflux, 71%

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BBr3

CHCl3

RT, 17 min, 91%

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